A clinically durable small diameter vascular graft may be achievable by optimizing the mechanical properties of an arterial bioprosthesis, as well as other biologically related characteristics. We believe that the molecular structure and supramolecular organization of native type I collagen and elastin fiber assembly establishes an important paradigm for the design of an arterial substitute composed of bio-inspired protein fiber analogues. Specifically, we intend to: (1) Determine the molecular level features of collagen and elastin fiber analogues that influence the mechanical behavior and physiochemical properties of protein-based fiber networks. Elastin and collagen analogues will be produced by biosynthetic and chemical schemes and processed into fiber networks by nanofabrication techniques. Both solution and solid state methodologies will be used to define material structure-property relationships. (2) Identify the micro scale characteristics of a protein fiber reinforced biopolymer composite that dictate mechanical responses relevant to the design of an arterial substitute. The mechanical behavior of both single and multicomponent fiber network composites will be investigated by static and dynamic mechanical testing under physiologically relevant conditions. In the process, constitutive mathematical models will be applied to assist in conduit design, as well as in the subsequent analysis of construct remodeling. (3) Define the morphological and structural remodeling of a collagen and elastin fiber reinforced vascular construct in vivo. Both acellular constructs, as well as conduits seeded with autogenous endothelial cells will be examined in a baboon animal model. Specifically, the effect of the local biological and mechanical environment on short- and long-term conduit properties, including patency and biostability will be defined. Lay summary: Optimizing mechanical and other biologically related properties may be an important step in the development of a small diameter arterial prosthesis critical to the fields of cardiac, plastic, and vascular surgery, as well as to the successful implantation of artificial organs and metabolic support systems.